In recent years, hyaluronic acid, which has excellent biocompatibility and also has many beneficial effects including a moisturizing effect, has been focused in the cosmetology field, the medical field and the like. Hyaluronic acid is a linear high-molecular-weight polysaccharide in which β-D-N-acetylglucosamine and β-D-glucuronic acid are bound alternately, and is known to distribute in connective tissues in mammals and also distribute in chicken's combs, streptococcal capsules and the like. Commercially available products of hyaluronic acid are generally prepared by the isolation/extraction from chicken's combs, umbilical cords or the like, a fermentation method using a microorganism such as a microorganism belonging to the genus Streptococcus, and the like.
Gel compositions each containing a high-molecular-weight material have been used conventionally in the cosmetology field, the medical field and the like. In particular, gel compositions which are intended to be used in the cosmetology field, the medical field and the like are applied to human bodies and therefore are required to have excellent biocompatibility. For these reasons, it has been considered to use hyaluronic acid, which is a naturally occurring material and has excellent biocompatibility, as a high-molecular-weight material to be contained in the gel compositions.
In Patent Document 1, for example, a method for preparing a gel composition using crosslinked hyaluronic acid is disclosed. In Patent Document 2, a gel of a photocrosslinkable hyaluronic acid derivative is disclosed, which is characterized in that 0.0005 to 0.05 piece on average of a photodimerizable crosslinking group is introduced per two hyaluronic acid-constituting sugar units. In Patent Document 3, a method for producing a crosslinked hyaluronic acid gel is disclosed, which is characterized by agitating/mixing a mixture comprising 10 W/V % or more of hyaluronic acid, a cross-linking agent and water under acidic or alkaline conditions.
However, as disclosed in Patent Documents 1 to 3, chemically modified hyaluronic acid is used in most of the conventional gel compositions prepared using hyaluronic acid. Therefore, the conventional gel compositions have a problem that the characteristic properties inherent in hyaluronic acid as a naturally occurring material are lost.
Furthermore, in Patent Document 4 for example, a method, for producing a hyaluronic acid gel is disclosed, which is characterized in that hyaluronic acid is allowed to co-exist together with both water in such an amount that the concentration of hyaluronic acid can become 5% by mass or more and an acid component in an equimolar amount to a carboxyl group in hyaluronic acid or more and the co-existing state is retained, thereby producing the hyaluronic acid gel. However, the hyaluronic acid gel produced in Patent Document 4 is poorly soluble in water, and therefore hyaluronic acid can be hardly eluted into water. Therefore, a poorly water-soluble hyaluronic acid gel as disclosed in Patent Document 4 is deteriorated in the effect induced by hyaluronic acid contained therein, i.e., impartment of moistness and springiness to skin, when applied onto skin, and therefore is improper for use in the cosmetology field and the like. Furthermore, the hyaluronic acid gel disclosed in Patent Document 4 is produced by allowing hyaluronic acid, an acid and water to stand for at least several days under low-temperature conditions, and therefore has a problem that a long period of time is required for the production of the hyaluronic acid gel.
In Patent Document 5 for example, a matter that a hyaluronic acid gel is produced by bringing a hyaluronic acid solution into contact with a water-soluble organic solvent, such as methanol, ethanol, isopropanol and acetone, under conditions having a pH value of 2.0 to 3.8 is disclosed. In the method disclosed in Patent Document 5, however, the water-soluble organic solvent is contained in a large amount in the hyaluronic acid gel, and therefore the hyaluronic acid gel has a problem that the hyaluronic acid gel is hardly used in the cosmetology field, the medical field and the like. In the cosmetology field, the medical field and the like, a sheet made from a gel composition is advantageous because the sheet can be applied onto skin easily. However, the hyaluronic acid gel disclosed in Patent Document 5 has an additional problem that the hyaluronic acid gel cannot be made into a sheet-like form easily by a simple method such as a cast method.